Abstract
ObjectivesWe investigated the involvement of the proteasome in the mechanism of preconditioning with hyperbaric oxygen (HBO-PC).MethodsThe experiments were performed on male Wistar rats subjected to a transient global cerebral ischemia of 5 min duration (2-vessel occlusion model) and preconditioned or not with HBO for 5 preceding days (1 h HBO at 2.5 atmosphere absolute [ATA] daily). In subgroups of preconditioned rats, the proteasome inhibitor MG132 was administered 30 min prior to each preconditioning session. Twenty-four hours and 7 days post-ischemia, after neurobehavioral assessment, the brains were collected and evaluated for morphological changes and quantitative immunohistochemistry of cell markers and apoptosis-related proteins.ResultsWe observed reduced damage of CA1 pyramidal cells in the HBO preconditioned group only at 7 days post-ischemia. However, both at early (24 h) and later (7 days) time points, HBO-PC enhanced the tissue expression of 20S core particle of the proteasome and of the nestin, diminished astroglial reactivity, and reduced p53, rabbit anti-p53 upregulated modulator of apoptosis (PUMA), and rabbit anti-B cell lymphoma-2 interacting mediator of cell death (Bim) expressions in the hippocampus and cerebral cortex. HBO-PC also improved T-maze performance at 7 days. Proteasome inhibitor abolished the beneficial effects of HBO-PC on post-ischemic neuronal injury and functional impairment and reduced the ischemic alterations in the expression of investigated proteins.SignificancePreconditioning with hyperbaric oxygen-induced brain protection against severe ischemic brain insult appears to involve the proteasome, which can be linked to a depletion of apoptotic proteins and improved regenerative potential.
Highlights
It has been postulated that hyperbaric oxygenation can be used as a preconditioning modality to increase the resistance of neurons to ischemia
Such depletion could be mediated by the ubiquitin-proteasome system that is activated upon HBOPC
Seven-day mortality equaled 30% both in the nonpreconditioned group and in the HBO preconditioned group (Figure 1A), while 33.3% mortality was noted in the MG132 group
Summary
It has been postulated that hyperbaric oxygenation can be used as a preconditioning modality to increase the resistance of neurons to ischemia. Hyperbaric oxygen preconditioning (HBO-PC) has been shown to provide neuroprotection in Proteasome and HBO Preconditioning several models of cerebral ischemia [3,4,5]. It has not been determined whether HBO-PC is effective against very severe global brain ischemia, in which systemic blood pressure is reduced to 30 mmHg, such as in the modified two vessel occlusion (2VO) cerebral ischemic model [6]. Regenerative capabilities of neural cells might become be enhanced following HBO-PC Whether this effect depends on proteasomes has not been determined. Changes in tissue expression of 20S core particle of 26S proteasome and those of nestin and proteins involved in cell death mechanisms were investigated in the brain across all groups
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